AzTrials
AzTrials

Pancreatic CancerPhase 1/2NCT03340974

Pilot Dose Escalation Trial of Stereotactic Body Radiation Therapy (SBRT) in Combination With GC4419 in Pancreatic Cancer

A Phase 1/2 study testing GC4419, Stereotactic Radiation Therapy (SBRT) 50 Gy and Stereotactic Radiation Therapy (SBRT) 55 Gy in people with Pancreatic Cancer and Stereotactic Body Radiation Therapy, run by Galera Therapeutics, Inc. at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of the phase I/II clinical study is to determine the best dose of fractionated stereotactic radiation therapy (SBRT) given either with Avasopasem manganese (GC4419) or placebo to patients who have been diagnosed with locally advanced pancreatic cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
GC4419, Stereotactic Radiation Therapy (SBRT) 50 Gy and Stereotactic Radiation Therapy (SBRT) 55 Gy
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
42 participants
Where
6 sitesUnited States
Study dates
12 Feb 2018to 26 May 2021
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Cytologic or biopsy confirmed adenocarcinoma of the pancreatic head, body or tail
  • Disease that is appropriate for SBRT by virtue of being:
  • Locally advanced and technicallyunresectable, as determined by a pancreaticobiliary surgeon as part of a multidisciplinary review at the investigative site, including multi-phasic CT demonstrating: i.Greater than 180 degree tumor involvement of the superior mesenteric artery ii. Greater than 180 degree tumor involvement of the celiac axis, including major branches of the celiac axis that render it unresectable (e.g. common hepatic artery).
  • Tumor involvement of the first branch of the SMA that is not surgically reconstructible iv. Long segment involvement of the superior mesenteric vein/portal vein or hepatic artery that is not surgically reconstructible b. Potentially resectable, but patient is judged not a candidate for surgery, after multidisciplinary review at the investigative site; c. Potentially resectable, but the patients refuses surgery and is considered an acceptable candidate for SBRT after multidisciplinary review at the investigative site; d. "Borderline" resectable, as determined by multidisciplinary review, including absence of distant lymphadenopathy and the primary tumor characterized by one of more of the following: i. A tumor-vessel interface (TVI) with the mesenteric vein (SMV) or portal vein (PV) measuring ≥180° of the circumference of either vein's wall or short-segment occlusion of either vein with a normal vein above or below the obstruction amenable to reconstruction; ii. Any TVI with the common hepatic artery (CHA) with normal artery proximal and distal to the TVI amenable to reconstruction; iii. A TVI with the superior mesenteric artery (SMA) measuring <180° of the circumference of the vessel wall
  • Pancreatic tumor size and limited bowel involvement by tumor must be judged acceptable for SBRT at the discretion of the treating investigator
  • No evidence of distant metastasis either prior to or after induction chemotherapy.
Show all 15Show fewer
  • Completion of at least 3 months of standard induction chemotherapy for LAPC, which should consist of either FOLFIRINOX, gemcitabine or nab-paclitaxel or another standard combination of induction chemotherapy agents
  • Patient must have metal stent in place if duodenal stent is required. If patient has plastic stent, this must be replaced prior to radiation.
  • Ability to understand and follow the breathing instructions involved in the respiratory gating procedure or to tolerate compression sufficient to reduce fiducial motion to <= 5mm.
  • Age 18 years or older
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (0, 1 or 2)
  • Adequate hematologic function as indicated by i. Absolute neutrophil counts (ANC) ≥ 1,500/mm3 ii. Hemoglobin (Hgb) ≥ 8.0 g/dL iii. Platelet count ≥ 75,000/mm3
  • Adequate renal and liver function as indicated by:
  • Creatinine ≤ 1.5 x upper-normal limit (ULN) ii. Total bilirubin ≤ 1.5 x upper-normal limit (ULN) iii. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN iv. Alkaline phosphatase ≤ 2.5 x ULN
  • Properly obtained written informed consent

Who cannot join

  • Prior radiation therapy to the abdomen that would overlap with treatment field
  • Prior surgical resection of pancreatic tumor
  • Receiving any approved or investigational anti-cancer agent other than those provided for in this study
  • Uncontrolled or active gastric or duodenal ulcer disease within 30 days of enrollment
  • Visible invasion of tumor into the lumen of the bowel or stomach on endoscopy (Note: Radiological infiltration into bowel is allowed, unless deemed clinically unsafe.)
  • Residual or ongoing ≥ Grade 3 non-hematologic toxicity from chemotherapy
Show all 16Show fewer
  • Contraindication to IV contrast
  • Concurrent participation in another interventional clinical trial or use of another investigational agent within 30 days of study entry Note: Patients who are participating in non-interventional clinical trials (e.g., QOL, imaging, observational, follow-up studies, etc.) are eligible, regardless of the timing of participation.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, renal failure, cardiac arrhythmia, or psychiatric illness that would limit compliance with treatment
  • Second primary malignancy within the last 5 years, unless treated definitively and with low risk of recurrence in the judgment of the treating investigator
  • Known history of HIV or active hepatitis B/C (patients who have been vaccinated for hepatitis B and do not have a history of infection are eligible)
  • Female patients who are pregnant or breastfeeding
  • Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for 30 days after the last dose of GC4419. This includes any woman who has experienced menarche but has not undergone successful surgical sterilization or is not postmenopausal (defined as amenorrhea for at least 12 consecutive months, or women on hormone replacement therapy with serum FSH levels greater than 35 mIU/mL. A negative urine or serum pregnancy test must be obtained within 14 days prior to the start of study therapy in all women of child-bearing potential.
  • Male subjects who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for up to 90 days after the last dose of GC4419 are excluded.
  • Requirement for concurrent treatment with nitrates or other drugs that may, in the judgment of the treating investigator, create a risk for a precipitous decrease in blood pressure.
  • Medical history that includes any condition, or requires the use of concomitant medications which, in the investigator's judgment, are associated with or create a risk of increased carotid sinus sensitivity, symptomatic bradycardia, or syncopal episodes.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Atlantic Health System / Morristown Medical Center

    Morristown, New Jersey, 07962

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: An Adaptive Phase I/II Dose Escalation Trial of Stereotactic Body Radiation Therapy in Combination With Radiomodulating Agent GC4419 in Locally Advanced Pancreatic Adenocarcinoma

The purpose of the phase I/II clinical study is to determine the best dose of fractionated stereotactic radiation therapy (SBRT) given either with Avasopasem manganese (GC4419) or placebo to patients who have been diagnosed with locally advanced pancreatic cancer.

Read the detailed description

This is a parallel arm adaptive design phase I-II dose-finding study to determine the optimal dose of fractionated stereotactic radiation therapy (SBRT), given either with the radiomodulating agent Avasopasem manganese (GC4419) or placebo for treatment of locally advanced pancreatic cancer. Dose-finding will be done using the sequentially adaptive phase I-II Late onset Efficacy-Toxicity (LO-ET) trade-off-based design [1-3].

A maximum of 48 patients will be randomized 1:1 to Arm A or Arm B. Patients in Arm A will receive Avasopasem manganese (GC4419) in combination with their assigned SBRT dose, and patients in Arm B will receive Placebo (PBO) with their assigned SBRT dose. The randomization will be restricted so that the sample size within each arm is exactly 24 patients.

GC4419/placebo will be given intravenously in a one hour infusion. SBRT must be initiated as soon as possible upon completion of the GC4419/placebo infusion.

GC4419/placebo will be given beginning on the first day of radiation and continuing daily, concurrent M-F throughout the administration of SBRT

Being tested
GC4419, Placebo, Stereotactic Radiation Therapy (SBRT) 50 Gy, Stereotactic Radiation Therapy (SBRT) 55 Gy
Keywords
Avasopasem manganese
Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GC4419Drug

    Also called Avasopasem manganese

    90 mg Avasopasem (GC4419) per day daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level

  • PlaceboDrug

    Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level

  • Stereotactic Radiation Therapy (SBRT) 50 GyRadiation

    Dose-finding will be done using the sequentially adaptive phase I-II Late onset Efficacy-Toxicity (LO-ET) trade-off-based design.

  • Stereotactic Radiation Therapy (SBRT) 55 GyRadiation

    Dose-finding will be done using the sequentially adaptive phase I-II Late onset Efficacy-Toxicity (LO-ET) trade-off-based design.

Study groups in NCT03340974
Study groupRoleWhat they receive
GC4419 90mg +50 Gy SBRTExperimentalAvasopasem manganese (GC4419) +SBRT
Receives: Drug: GC4419; Radiation: Stereotactic Radiation Therapy (SBRT) 50 Gy
GC4419 90 mg + 55 Gy SBRTExperimentalAvasopasem manganese (GC4419) +SBRT
Receives: Drug: GC4419; Radiation: Stereotactic Radiation Therapy (SBRT) 55 Gy
Placebo + 50 Gy SBRTPlacebo comparatorPlacebo +SBRT
Receives: Drug: Placebo; Radiation: Stereotactic Radiation Therapy (SBRT) 50 Gy
Placebo + 55 Gy SBRTPlacebo comparatorPlacebo + SBRT
Receives: Drug: Placebo; Radiation: Stereotactic Radiation Therapy (SBRT) 55 Gy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. CTCAE Grade 3 or 4 Gastro-intestinal (GI) Toxicities or Death Within 90 Days From the Start of Therapy

    Number of Common Terminology Criteria Adverse Events (CTCAE) that are grade 3 or 4 gastro-intestinal (GI) toxicities or deaths. CTCAE grade 3 or 4 gastro-intestinal toxicities are those adverse events that a subject may experience in their gastro-intestinal system that have been graded by the treating investigator to be severe (Grade 3) or life-threatening (Grade 4).

    Measured: Within 90 days from the start of therapy "related" after CTCAE

  2. Radiographic Stable Disease (SD) or Better Based on RECIST Criteria

    Per Response Evaluation Criteria In Solid Tumors (RECIST) criteria for target lesions that are assessed by radiographic imaging : Complete Response (CR) is the disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in the longest diameter of the target lesions; Stable disease (SD) is neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for local progressive disease (LPD); Local Progressive Disease (LPD) is at least a 20% increase in the longest diameter of the target lesion, utilizing the baseline measurement as reference.

    Measured: All subjects assessed with at least 12 months of follow up following the administration of SBRT

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Nov 2017
  2. Study start12 Feb 2018
  3. Primary completion21 Aug 2020
  4. Study completion26 May 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03340974
Sponsor's protocol ID
GTI-4419-101
Status last verified
Jan 2023
First submitted
8 Nov 2017
Last updated
15 Dec 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Hoffe S, Frakes JM, Aguilera TA, Czito B, Palta M, Brookes M, Schweizer C, Colbert L, Moningi S, Bhutani MS, Pant S, Tzeng CW, Tidwell RS, Thall P, Yuan Y, Moser EC, Holmlund J, Herman J, Taniguchi CM. Randomized, Double-Blinded, Placebo-controlled Multicenter Adaptive Phase 1-2 Trial of GC 4419, a Dismutase Mimetic, in Combination with High Dose Stereotactic Body Radiation Therapy (SBRT) in Locally Advanced Pancreatic Cancer (PC). Int J Radiat Oncol Biol Phys. 2020 Dec 1;108(5):1399-1400. doi: 10.1016/j.ijrobp.2020.09.022. Epub 2020 Nov 18. No abstract available.

    PubMed 33427657

  • Taniguchi CM, Frakes JM, Aguilera TA, Palta M, Czito B, Bhutani MS, Colbert LE, Abi Jaoude J, Bernard V, Pant S, Tzeng CD, Kim DW, Malafa M, Costello J, Mathew G, Rebueno N, Koay EJ, Das P, Ludmir EB, Katz MHG, Wolff RA, Beddar S, Sawakuchi GO, Moningi S, Slack Tidwell RS, Yuan Y, Thall PF, Beardsley RA, Holmlund J, Herman JM, Hoffe SE. Stereotactic body radiotherapy with or without selective dismutase mimetic in pancreatic adenocarcinoma: an adaptive, randomised, double-blind, placebo-controlled, phase 1b/2 trial. Lancet Oncol. 2023 Dec;24(12):1387-1398. doi: 10.1016/S1470-2045(23)00478-3.

    PubMed 38039992

  • Sishc BJ, Ding L, Nam TK, Heer CD, Rodman SN, Schoenfeld JD, Fath MA, Saha D, Pulliam CF, Langen B, Beardsley RA, Riley DP, Keene JL, Spitz DR, Story MD. Avasopasem manganese synergizes with hypofractionated radiation to ablate tumors through the generation of hydrogen peroxide. Sci Transl Med. 2021 May 12;13(593):eabb3768. doi: 10.1126/scitranslmed.abb3768.

    PubMed 33980575

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing GC4419, Stereotactic Radiation Therapy (SBRT) 50 Gy and Stereotactic Radiation Therapy (SBRT) 55 Gy in people with Pancreatic Cancer and Stereotactic Body Radiation Therapy, run by Galera Therapeutics, Inc. at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

CTCAE Grade 3 or 4 Gastro-intestinal (GI) Toxicities or Death Within 90 Days From the Start of Therapy (time frame: Within 90 days from the start of therapy "related" after CTCAE). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03340974, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in